Artemisianins A-D, new stereoisomers of seco-guaianolide involved heterodimeric [4+2] adducts from Artemisia argyi induce apoptosis via enhancement of endoplasmic reticulum stress

Bioorg Chem. 2019 Mar:84:295-301. doi: 10.1016/j.bioorg.2018.11.013. Epub 2018 Dec 1.

Abstract

Artemisianins A-D (1-4), four stereoisomers of sesquiterpenoid dimers, forming via [4+2] cycloaddition from a 1, 10-seco-guaianolide dienophile and a guaianolide diene, along with two biosynthetically related precurors 5 and 6, were isolated from the famous traditional Chinese medicine Artemisia argyi. The structures of 1-4, including their absolute configurations, were elucidated by extensive spectroscopic data and ECD/TDDFT calculation analysis. Compounds 1-4 exhibited cytotoxicity with IC50 values ranging from 7.2 to 23.3 μM. The accumulation of Ca2+ in cytoplasm and enlarged endoplasmic reticulum (ER) indicated that 1 mediated HT-29 cancer cell apoptosis through improvement of ER-stress, which was further proved by unfolded protein response (UPR) pathway on basis of the upregulation of IRE1α, p-PERK, ATF6, and CHOP.

Keywords: Artemisia argyi; Endoplasmic reticulum stress; Seco-guaianolide sesquiterpenoid dimer; Stereoisomer; Structure elucidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • Artemisia / chemistry*
  • Artemisia / metabolism
  • Cell Line, Tumor
  • Dimerization
  • Endoplasmic Reticulum Stress* / drug effects
  • Humans
  • Medicine, Chinese Traditional
  • Molecular Conformation
  • Plant Leaves / chemistry
  • Plant Leaves / metabolism
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology
  • Stereoisomerism

Substances

  • Sesquiterpenes